A fundamental question in mental health disorders is how environmental signals experienced early in life may have long-lasting effects on the development of disease in human populations. Light signals have long been recognized as a powerful environmental influence on the development of specific brain regions and functions. In animal models, perinatal light cycles are transmitted from mother to fetus through melatonin signaling, and have persistent effects later in life on stability of the biologic clock and the expression of depression and anxiety behaviors in adulthood, establishing that light is an environmental signal with enduring epigenetic effects on brain circuits and behavior. We propose to test a set of novel hypotheses in reference to a class of diseases for which light cycles are a key factor - anxiety, depression, and suicide. Using as our platform the two Nurses Health Study (NHS) cohorts, NHS and NHS2, which contain the birth dates, locations, health profiles, shift work histories and stress data of ~238,000 US nurses, we seek to determine whether exposure to light cycles around the time of birth (as inferred from birth date and location) can modulate the risk of these disorders and/or interact with shift work as a marker for disruption of the biologic clock. Further, we will test the stress-diathesis model by evaluating novel hypothesis in which fetal photoperiodic programming represents a sensitizing event making our study participants more vulnerable to the development of affective disorders in response to stressful events. If epidemiological patterns of affective disorders are established in this exploratory R21 study with limited budget and duration, then a follow-on R01 study could examine specific gene X environment interactions and signaling mechanisms underlying an established environmental risk factor for affective disorders. By examining light exposure in the womb, we seek to expand current research paradigms related to light signals and affective disorders, by shifting the attention to a much earlier time period in life than thus far has been studied - in utero. If our hypotheses are correct, study results will change clinical practice paradigms, as they relate to counseling of pregnant women to help guard against the development of depression and anxiety disorders in their children and translate to practical and explicit, but safe and incredibly inexpensive, interventions. Recommendations may involve the time pregnant women spend outdoors in order to increase their exposure to daylight, depending on latitude of their residence and projected birth date. Alternatively, they could entail exposure to higher-lux light lamps at specified times of the day, when indoors.